Spectrum and Prevalence of BRAF Mutations in Thyroid Tumors
MN Nikiforova, RR Seethala, SI Chiosea, NP Ohori, YE Nikiforov. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: Papillary carcinoma (PC) is the most common type of thyroid malignancy. BRAF mutations are found in 40-45% of these tumors and serve as an unfavorable prognostic marker. In addition to the most common point mutation, BRAF V600E, several other mutations in this gene have been reported. In this study, we investigate the spectrum and prevalence of BRAF mutations detected in a large series of thyroid tumor samples.
Design: We analyzed 324 thyroid tumors, including 242 papillary carcinomas (PC), 39 follicular carcinomas (FC), and 43 follicular adenomas with atypical nuclear features present focally and not sufficient for the diagnosis of PC (FAA). DNA was isolated from fleshly frozen tissue (32 samples) or paraffin-embedded tissue (292 samples). Mutations in codon 600 and adjacent codons of the BRAF gene were detected by real-time PCR and post-PCR melting curve analysis on LightCycler (Roche). Direct nucleotide sequencing on ABI 3130 (Applied Biosystems) was used to confirm the mutation type.
Results: BRAF mutations were identified in 97 (40%) of PC and in none of FC and FAA. Of 97 mutations, 95 (98%) were the most common BRAF V600E mutation, one was a BRAF A1801G (K601E) point mutation and one was a novel complex mutation BRAF T599I, I599_V600insL. Among tumors with BRAF V600E mutation, 74% were classic PC, 15% were tall cell variant of PC, and 7% were follicular variant of PC. The tumor with BRAF K601E mutation was a follicular variant of PC and the tumor with BRAF T599I, I599_V600insL mutation was a solid variant of PC.
Conclusions: Although V600E accounts for the vast majority of all BRAF mutation in thyroid tumors, about 2% of unusual BRAF mutations can be found, including a novel BRAF T599I, I599_V600insL mutation identified in the solid variant of PC. In this series, all types of BRAF mutation were specific for PC and were not found in nodules with slightly atypical nuclear features.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 85, Tuesday Afternoon